INTRODUCTION:

Plants have provided mankind an enormous variety of potent drugs to ease the sufferings from various diseases, globally. Medicines prepared out of herbs form the basis of about 75-80% of the world’s population mainly in developing countries because of their better compatibility and lesser side effects. Hence, there is a growing interest in the pharmacological evaluation of various plants used in traditional Indian system of medicine.

Siddha system of medicine, which is the traditional heritage science of Tamil origin, renders the application of numerous medicines based on plants, minerals-metals and animal origin.

The treatment modality in Siddha intensely states the usage of plant-based drugs as the first line of treatment for any type of illness. This can be revealed from the classical Siddha maxim, “வேர் பாரு தழை பாரு மிஞ்சினக்கால், மெல்ல மெல்ல பற்ப செந்தூரம் பாரே”, (Vēr pāru thaṙai pāru miñcinakkāl, mella mella parpa centūram pārē )¹. Hence it can be understood that the plant-based drugs are used prior to the metals and minerals based drugs. The selection of drugs in Siddha solely depends on the suvai (taste), panchabootham (five prime elements) and mukkuttram (three humors) in accordance with the disease manifestations. Hence, every formulation has specified therapeutic action according to the taste contained in it, which overwhelms the imbalance of three humors responsible for disease condition. Vatham, Pitham and Kabam are the three humors in the human body, which are responsible for the normal functioning when maintained in equilibrium².

Brief description about Kudineer (Decoction) in Siddha system of medicine:

Kudineer is also named as Kiyazham, Kashayam, Unneer, Marundhu neer, Vaai kudithidum punal. It is prepared by adding specific proportion of water (according to the total weight of raw materials) to dry herbs or fresh ones, which are coarsely powdered and then boiled to reduce the contents to 1/16^th or 1/8^th or 1/4^th or 1/2 of the initial volume and filtered for use³. The filtrate is known as Kudineer. It is one among the 32 types of internal medicines mentioned in Siddha system of medicine. The shelf life of this form of medicine is one saamam (three hours) and hence it should be consumed within the specified period from the time of preparation¹. There are two types of Kudineer viz. Ooral kudineeer (prepared after soaking the contents overnight) and Kodhi Kudineer (prepared by boiling). It is a general rule that the volume of water added is 16 times the weight of raw drugs. Thus, the medicinal value and therapeutic efficacy of the filtrate varies according to the reduction ratio from the total quantity of contents and the total volume of water added. This is one of the distinctive principles of Siddha pharmacology adopted for various therapeutic purposes such as instillation, external wash, gargling, drinking, wound cleaning, purgation, enema, diaphoretic and douche. Hence decoctions can be used both internally and externally according to the disease condition and experience of clinicians^4,5. As a whole, decoctions are water-based extracts of either herbal, herbo-mineral or animal-based ingredients which are easily absorbed into the body and enter into the blood stream rapidly for better efficacy³.

Neermulli kudineer (NMK) is a classical Siddha polyherbal formulation, which has been used in Siddha system of medicine remarkably for clinical conditions such as Peruvayiru (Ascites), Veekkam (Inflammation), Oothal (Oedema), Neerkattu (Absolute urinary retention or suppression of urine) and Sobai rogam (associated complications followed by Anaemia)^6,7,8. These are mainly due to the vitiated Vatham and increased Pitham and Kabam humor resulting in the accumulation of interstitial fluids in our body⁹. All these clinical conditions can be seen predominantly in renal diseases, cardiovascular diseases, liver and spleen pathology, tumor and anemia. Obviously, all these conditions entail the intervention of diuretics for the preliminary management. NMK has been used as a potent diuretic in Siddha system of medicine by the traditional clinicians. As a diuretic, NMK promotes the removal of excess water, salts, poisons, and accumulated metabolic products from the body by increasing the urinary flow and volume. Also, it helps to lower high blood pressure, reduce fluid retention, oedema and provide relief from the pain and burning sensation. There is no evidence of pharmacological and clinical studies conducted so far to prove the efficacy of Neermulli kudineer as a formulation. Hence the ingredients of Neermulli Kudineer are reviewed here with Siddha perspectives along with therapeutic uses, phytochemical constituents and through various literatures based on scientific studies carried out, which ultimately may enlighten the researchers to conduct further scientific studies and clinical research in this polyherbal decoction.

The preparation of NMK decoction has been mentioned in the classical Siddha literature Siddha Vaithiya thirattu/ Siddha Formulary of India- Part I, Volume I, Ministry of AYUSH, Govt. of India, as given below;

Ingredients:

1. Nerunjil samoolam

2. Nelli vattral

3. Neermulli samoolam

4. Parangipattai

5. Manathakkali vattral

6. Sarakkondrai puli

7. Sombu

8. Vellari vithai

9. Surai kodi

10. Kadukkai thol

11. Thandrikkai thol

METHOD:

The above said drugs are cleaned and weighed each one varaagan (4.1gm) and coarsely powdered. According to Kudineer vithi, water is added to the ingredients and allowed to boil well and get it reduced and filtered. This can be administered ½ aazhakku (80 ml) twice daily for the above mentioned diseases. The preparation of Neermulli Kudineer is also mentioned in the name of Nerunjil Kudineer in Siddha literatures^{7, 8}.

Review of ingredients of NMK in Siddha literatures^10,11:

1. Nerunjil - Tribulus terrestris L.

Synonyms: Thirikandam, Thirikandakam, Thirithandam, Nerunjipadham, Asuvasattiram, Suvathattam, Kokandam, Kaamarasi, Suvathukandam, Kittiram, Kondam, Sudham, Yaanaivanangi.

Properties:

Suvai (Taste)-Thuvarppu, Inippu; Thanmai (Character) - Thatpam; Pirivu (Division)- Inippu.

There are two types, viz. small caltrops and big caltrops or Yaanai nerunjil (Pedalium murex). The whole plant can be used for medicinal purpose to treat various ailments like dropsy, renal stones, burning and painful micturition, excessive heat and thirst, dysuria, leucorrhoea, erectile dysfunctions, chronic cystitis, impotence, gonorrhea and urinary incontinence. It is effectively prescribed for the inflammatory conditions of urinary tract. The seeds of this plant along with Piper cubeba, purified salt of potassium nitrate and Mesua ferrea are indicated for the treatment of oedema due to cardiac diseases. The dried fruits and roots, boiled with raw rice and made into porridge form are given for leucorrhoea and painful micturition. The combination of Nerunjil, Lavangam (Syzygium aromaticum), Yelakkai (Eletteria cardomum) and sugar along with Aya chenduram (an higher order Siddha formulation) is indicated for jaundice.

2. Nelli vattral – Phyllanthus emblica L.:

Synonyms:

Amalakam, Aalakam, Aambal, Aamarikam, Dhathari, Dhathiri, Korangam, Mirudhupala, Meedhunthu.

Properties:

Suvai - Pulippu, Thuvarppu, Inippu; Thanmai - Thatpam; Pirivu - Inippu.

The dried fruits of this tree are named as Nellimulli, which are black in colour. All the parts of the tree possess medicinal properties which are beneficial in conditions like nausea, tastelessness, vertigo, constipation and diseases of kabam. The roots, seeds, stem bark and fruit (both fresh and dried) of this tree are consumed for diseases such as ascites, anemia, liver disorders, excessive heat, hemorrhoids, menorrhagia, epilepsy and painful conditions as per the karpa vidhi indicated in Siddha literatures. It is one of the Kaya karpa medicines (a specialized methodology of rejuvenation in Siddha science) which can be taken for the normal maintanence of our body free from diseases. The unriped and dried fruits are effective in the management of nausea, fatigueness, thirst and anorexia and vomiting. Medicines prepared from Phyllanthus emblica include Nellikai legiyam which is given for jaundice, anemia, oedema, peptic ulcers and dysuria. Nellikai thylam, which is taken as bathing oil in the conditions of eye diseases, peripheral neuritis and pittha diseases. Nellimulli legiyam and Kudineer are also prepared with this.

3. Neermulli – Asteracantha longifolia L. Nees

Synonyms:

Nidhakam, Ikkuram, Kaakandam, Thuragadhamoolam, Mundakam.

Properties:

Suvai- Inippu, Siru kaippu; Thanmai – Thatpam; Pirivu – Inippu.

Siddha literature emphasizes A.longifolia as a potent diuretic and is a small shrub grown in marshy lands. The whole plant parts are of medicinal value. The seeds of this plant are effective in oedematous conditions, diarrohea, leucorrhoea and male infertility conditions. The whole plant is given for the treatment of dropsy, ascites, anemia, and inflammatory conditions. The soaked water of dried plant is given for obesity, anemia and ascites. The plant decoction can be dispensed as an adjuvant for various diuretic medicines in Siddha system so that it clears the excessive unwanted fluids accumulated in the body and cures the diseases of genito-urinary system through effective excretion of urine. It also helps in constipation. The seeds are predominantly used as one of the ingredients in aphrodisiac medicines and improvise the fertility.

4. Parangipattai – Smilax china L.

Synonyms:

Madhusmigam, Madhusmeegi, Seenapattai, Parangichakkai.

Properties:

Suvai - Inippu; Thanmai - Thatpam; Pirivu - Inippu.

The decoction and powdered root tuber of this plant are effective in the management of skin diseases, nausea, hemorrhoids, carbuncles, diabetes, diseases of vatham, rheumatism, scabies and syphilitic ulcers. Parangipattai rasayanam, Parangipattai chooranam, Parangipattai legiyam and Parangipattai pathangam are some of the medicines prepared out of this root tuber which are administered for leucorrhoea, gonorrhoea, chronic ulcers and scrofulary painful inflammatory conditions and diseases of kabam.

5. Manathakkali – Solanum nigrum L.

Synonyms:

Manithakkali, Milaguthakkali, Ulagamatha, Vidaikantham, Vaayasam, Kaakamaasee.

Properties:

Suvai - Inippu; Thanmai - Thatpam; Pirivu - Inippu.

The fruit and leaves are of medicinal value. It is exclusively handled for oral ulcers (stomatitis) and given for patients who are suffering from chronic illness to improvise the health. It is also one of the Kaya karpa medicines consumed for the longevity of life as mentioned in Siddha literatures. The decoction (35- 80ml) of dried fruits is prescribed for diseases of kabam and vatham, stranguary and is a good laxative. Consumption of 35ml of leaf juice produces diuresis and relieves the oedema, ascites and oral stomatitis. The dried fruits are fried with ghee and can be consumed for nausea and phlegm. Oil prepared from the dried fruit is prescribed for respiratory problems.

6. Sarakkondrai - Cassia fistula L.

Synonyms:

Kondrai, Konnai, Perunkondrai, Kiruthamalam, Dhamam, Madhalai, Idhazhi, Kadukkay, Aakkuvatham.

Properties:

Suvai - Pulippu, Inippu; Thanmai - Veppam; Pirivu - Kaarppu.

The leaves, flowers, dried fruit pulp, seeds, stem bark and root bark are used medicinally for various purposes. The dried fruit pulp is renowned for its purgative action and effective in the management of leucorrhoea, constipation and intestinal problems. It is a safer laxative when given in minimal doses even in pregnant women and children. For the arthritic inflammations, this can be applied externally and the same is effective for abdominal pain and constipation in children and relieves the flatulent colic with soft motions and cures urinary retention. Traditional application of the fruit pulp along with salts of potassium nitrate, borax or potash alum, dried ginger, Embelia ribes and Asafoetida powder is effective in the management of oliguria and anuria.

7. Sombu - Foeniculum vulgare Mill.

Synonyms:

Perunseerakam, Venseerakam.

Properties:

Suvai - Kaarppu, Inippu; Thanmai - Veppam; Pirivu - Kaarppu.

The dried and riped fruits are used for abdominal discomfort, fever, indigestion, flatulence, acid peptic disease, respiratory problems, sore throat, rhinitis and uterine disorders. A hot infusion of the fruit is useful in amenorrhoea and in cases of decreased sweating. It is effective in the management of dysmenorrhoea and is also a good appetizer. Sombu theneer and Sombu thylam are some of the medicines prepared out of F. vulgare in Siddha system of medicine.

8. Vellari - Cucumis sativus L.

Synonyms:

Uruvaaram, Oorvaruham, Karkati, Mirundhu.

Properties:

Suvai - Inippu; Thanmai - Thatpam; Pirivu - Inippu.

In Siddha system of medicine, there are specified indications for the plant parts of Cucumis sativus. The unriped tender fruit, unriped and riped fruit, seeds and leaves possess precise properties. The unriped tender fruit balances the imbalanced three humors. The unriped fruit is indicated for skin problems, oliguria, excessive thirst and urethral itching. It increases the vatham humor and appetite. The fruits increase the kabam humor. The seeds are exclusively indicated for stranguary, renal calculi, urethral stricture, leucorrhoea, burning micturition and fissures in the urinary tract. Also, the seeds are supplemented with other diuretic Siddha formulations and in medicines for erectile dysfunction. For throat infections, the leaves are powdered and consumed with cumin seeds. It also produces effective diuresis.

9. Surai – Lagenaria siceraria (Mol) Standl.

Synonyms:

Sorai

Properties:

Suvai - Kaippu; Thanmai- Thatpam; Pirivu - Inippu.

It is a climbing plant and there are two varieties viz, sweet bottle gourd and bitter bottle gourd. The bitter one is mentioned as Kaatu Surai, Pei Surai (wild variety). The fruit pulp, leaves, climbing stem is of medicinal value and are consumed for its diuretic and cooling effct. The wild variety is bitter, emetic, cathartic and drastic purgative like colocynth which may lead to fatal due to dehydration. The tender leaves are used for effective diuresis and thereby reduce the oedema and inflammation. The unriped fruit part when consumed as whole results in liver and spleen disorders, cardiac problems, tastelessness and it increases the vatham and Pitham humor. The leaves and climbing stem are exclusively handled for its diuretic action in the management of delirium, urinary retention, jaundice, ascites and oedema and are supplemented with other Siddha formulations possessing diuretic effect. The fruit pulp is externally applied for headache and burning sensation of hands and feet. The fully matured riped fruit part becomes shell like and the burnt ashes of the shell are advised for mercurial toxicity and can be applied externally with honey for night blindness and scrofulary swellings.

10. Kadukkai – Terminalia chebula Retz.

Synonyms:

Akkodam, Anganam, Andhan, Aparanam, Abaiyan, Amaritham, Amalai, Amutham, Ammai, Amrutha, Arabi, Arithaki, Aliyan, Avviyatha, Resaki, Yemavathi Iyavi, Haimavathi, Kadu, Kaayastha, Siyirutham, Sirayahi, Sirottam, Siva, Sethaki, Sathanika, Seya, Dhivya, Devi, Nandhari, Nechi, Patthiyam, Paariyam, Pishakvara, Boothana, Boothan, Prabathya, Praanatha, Megam, Vayadaram, Vayastha, Varikkai, Vanadurgi, Vijayadevan, Rohini, Jivanika, Jeevanthi, Jeevapriya, Jeevya, Jeya.

Properties:

Suvai - Mainly Thuvarppu, Siru Inippu, Kaippu, Kaarppu, Pulippu; Thanmai - Veppam, Pirivu - Inippu.

Kadukkai is one of the Kaya Kalpa medicines in Siddha system of medicine. The riped fruit shell devoid of seeds is called Kadukkai thol and is of much medicinal importance. The seeds may produce some toxic effects and should not be consumed. Powdered shell of the riped fruit is exclusively consumed for its digestive and laxative action and for the prevention of diseases to increase the longevity of life and premature greying of hair. It is an effective astringent and hence advised for bleeding conditions in case of sinusitis, hemorrhoids, menorrhagia and dysentery. The formulations such as Kadukkai legiyam, Kadukkai Nei, Kadukkai chatthu, Kadukkai vadagam and Bhavana kadukkai are traditionally used in Siddha for diseases such as abdominal pain, inflammation, anemia, oedema, anuria, constipation, hypertension and diabetes. Kadukkai Karpam, a specialized form of preparation is mentioned for the treatment of jaundice when consumed with prior caution.

11. Thandrikai – Terminalia bellerica (Gaertn).Roxb.

Synonyms:

Akkantham, Akkaathan, Amudham, Ambalathi, Aaramam, Erikatpalam, Kandhakatpalam, Kandhukan, Koolithurumam, Kalanthoondri, Sagadham, Thaabamaari, Vaandhiyam, Vitthiyam, Vibeethagam, Thirilingam, Boothavasagam, Thaanikkai.

Properties:

Suvai - Thuvarppu; Thanmai - Veppam; Pirivu - Inippu.

In Siddha system of medicine, the fruit rind of T.chebula is extensively used for its astringent and expectorant action. The decoction of the dried fruit is indicated for bronchial asthma. It is an effective medicine for the improvisation of vision. The dried fruit rind of T.chebula are powdered and administered with honey for Herpes infections. It has an excellent wound healing property and it cures the diseases of vatham and Pitham and advised for hypertension, leucorrhoea and penile ulcers.

The therapeutic actions and uses in Siddha system of medicine for the ingredients of NMK are discussed in Table 1.

Pharmacological review of ingredients of NMK:

1. Nerunjil - Tribulus terrestris L.

Antihypertensive and hematological effects:

Niemat Ahmed et al, 2015, evaluated the effect of Tribulus terrestris for the hypotensive and hypertensive effects. When it was administered at a dose level of 100 and 50mg/kg body weight of rats, the aqueous extract of Tribulus terrestris exhibited significant hypotensive effects on hypertensive rats through arterial smooth muscle contraction and membrane hypopolarization. They also evaluated that there is a reduction in mean corpuscular volume level of treated group when administered in high doses. Despite the curative effect, the researchers concluded that it might cause microcytic anemia when administered chronic¹⁴. Another study reported that the aqueous extract of T. terrestris showed a significant antihypertensive activity in renin-dependent 2-kidney 1-clip (2K-1C) model of hypertension and this might be related to its inhibitory effect on angiotensin converting enzyme (ACE) activity¹⁵.

Antimicrobial activity:

Saravanan singh et al, 2016, reported the antibacterial effect of Tribulus terrestris using various extracts on microorganisms and concluded that there was significant zone of inhibition for Pseudomonas aeruginosa, Klebsiella pneumoniae at 75% and 100% with increased concentration. Also, they have reported that Tribulus terrestris exihibited significant antifungal activity for Aspergillus niger, Trichoderma viridae, Microsporum gypseum and Candida albicans by disc diffusion method, stroke method and Agar well disc diffusion assays¹⁶.

Antiurolithiatic and Diuretic activity:

Chitra devi et al, 2017, conducted an in vitro study to evaluate the antiurolithiatic effect of Tribulus terrestris and Pedalium murex using artificial urine. They found that at a concentration of 2600 μg/ml, Tribulus terrestris exhibited maximum inhibitory level (81.3%) of crystallization, aggregation and nucleation of calcium oxalate crystals¹⁷. Another study done by Al-Ali et al , 2003, in Wistar rats and Guinea pig for the diuretic and contractile effects of Tribulus terrestris and found that the aqueous extract of T.terrestris produced positive diuresis with increased concentrations of Na⁺, K⁺ and Cl^-in the urine¹⁸. Hariprasth et al, 2013, also elucidated the antiurolithiatic activity of T.terrestris in rats induced with ethylene glycol and the results were significant (P<0.01) in the reduction of urea, creatinine and uric acid levels, increased urinary output and decreased calcium oxalate crystals. Also the extract of T.terrestris prevented the renal tissue damage¹⁹.

Immunomodulator activity:

Kranthi Raju et al, 2016, subjected the methanolic extracts of T.terrestris to study the immunological effects using phagocytic test, carbon clearance test, delayed type hypersensitivity response, T- cell population test and drug induced myelosuppression test. The researchers found it to be a potent immunostimulatory drug against the cyclophosphamide with improvement in hematological parameters and found to be less immunosuppressive with some parameters²⁰. Also, T.terrestris is one among the patternized herbal nanoparticles and hence it can be used in the treatment of various chronic diseases with higher bioavailability and potency.²¹

Hepato - Nephroprotective activity:

Abdel Kader et al, 2016, evaluated the nephroprotective and hepatoprotective activity of T.terrestris against CCl₄induced toxicity. The test extract showed a dose dependant effect and highly significant in the reduction of urea and creatinie levels. The histopoathological study supported the plant extract to be protective against CCl_4. But there was a weak positive effect in the elevated liver enzymes and hence found to be less hepatoprotective²². Ismaiel et al, 2017, investigated the T.terrestris extracts against Ivermectin induced hepato-renal toxicity in rabbits. Histologically, ethyl acetate extract of Tribulus terrestris markedly improved hepatic architecture, meanwhile ethanol extract of Tribulus terrestris revealed substantial renal improvement. The biomarker ezymes AST, ALT, ALP, Urea and creatinine were also much decreased²³. Sudhanshu Kumar Meher et al, 2016, studied the aqueous extract of Tribulus terrestris Linn fruit and Crataeva nurvala Buch-Ham stem bark in experimentally induced nephrotoxicity with Gentamicin. They studied at different dose levels in pre and post treatment. It was observed that the trial drugs were found effective in reducing the renal parameters such as urea, creatinine and uric acid levels. Also the cellular matrix had also got repaired in the affected group.²⁴

Antioxidant activity:

T. terrestris reduced the levels of free radicals responsible for lipid peroxidation, and thus decreased the level of malondialdehyde, end product of lipid peroxidation. T. terrestris had the potential of scavenging free radicals and reduced the oxalate-induced free-radical damage. The rebalancing of elevated antioxidant enzymes, viz SOD and GST and their gene expression by T. terrestris treatment further substantiated the protective nature of this plant extract against free radical-induced oxidative stress. Also, T. terrestris treated hyperoxaluric animals restored the normal morphology of glomeruli and had the potential to normalize the peroxidant status and gene expression of antioxidant enzymes²⁵.

Spermatogenic effect:

Karimi Jashni et al, 2012 investigated the effect of T. terrestris extract on the primary spermatocyte in wistar male rats for the spermatogenic effect. The researchers found that T. terrestris could probably balance the functions of the male reproductive system and might be used in the treatment of male infertility with increase in the number of primary spermatocytes. The studies showed that T. terrestris also increased the secretion of luteotropic hormone from pituitary gland due to the containing saponins²⁶.

2. Neermulli - Asteracantha longifolia, Hygrophila spinosa:

Antiurolithiatic activity:

Ingale et al, 2012, evaluated the antiurolithiatic effect of Hygrophila spinosa on CaOx induced nephrolithiatic rats. The animal groups treated with methanolic extract of H.spinosa revealed remarkable changes in urinary output, uric acid and oxalate crystal levels. There was a significant (P < 0.01) decrease in the levels of oxalate and calcium excretion, and restored the magnesium levels with potent antilithiatic property against the standard drug²⁷. The antilithiatic effect of aqueous extract of Hygrophila spinosa was determined by Sathish et al (2010) on ethylene glycol induced lithiasis in male albino rats for a period of 28 days. The urinary ionic parameters such as calcium, oxalate, inorganic phosphate, protein concentrations were reduced significantly (P<0.01). The elevated serum creatinine levels of lithiatic rats were reduced by prophylactic and curative regimen of extract treatment²⁸.

Diuretic activity:

Preethi et al, 2012, investigated the diuretic properties of the seeds of Hygrophila auriculata in normal wistar albino rats against the standard drug Frusemide, a high ceiling diuretic. There was a significant increase (P < 0.001) in sodium (198.33 ± 2.99 m.mol/L), potassium (97.67 ± 2.33 m.mol/L) and chloride ion excretion (132.67 ± 2.65 m.mol/L) in the 500mg/kg alcohol extract as compared to control group (107 ± 2.11 m.mol/L, 55 ± 4.09 m.mol/L and 87.33 ± 2.33 m.mol/L respectively). Also it induced both marked natriuresis and kaliuresis but the Na⁺/ K⁺ratio was more than that of frusemide, indicating the weak kaliuresis or K⁺ saving property of the extract. The diuretic and soothing properties of the plant were probably due to the potassium salts and large extent of mucilage present in the plant²⁹.

Antimicrobial activity and Antioxidant activity:

Kawsar et al, 2012, demonstrated the antifungal and antibacterial activity of methanolic extract of Asteracantha logifolia against the standard drugs ciprofloxacin and fluconazole. There was a significant zone of inhibition ranging from 15.0 to 26.0 mm. The maximum inhibitory concentrations of the plant extract were found to be 31.25 μg/ml against B. cereus, S. typhi, Sh. Sonnei, V. cholerae and A. niger ³⁰. Antimicrobial and radical scavenging potential of different palnt parts of A.longifolia evaluated by Ashwini et al (2014), explained that the high level of phenolic content of root, fruit and leaf extract of A. longifolia estimated by FCR method revealed the positive effect on oxidative stress through its radical scavenging activity. The extracts inhibited Gram positive bacteria to higher extent than Gram negative bacteria. Poisoned food technique was also performed to investigate antifungal activity against the fungi Colletotrichum capsici and Sclerotium rolfsii. The colony diameter of test fungi was considerably lesser in plates poisoned with extracts when compared to control plates. Among fungi, higher susceptibility was observed in case of S. rolfsii than C. capsici³¹.

Hepatoprotective activity:

Raj et al, 2010, investigated the in vitro and in vivo hepatoprotective effects of the total alkaloid fraction of Hygrophila auriculata leaves against CCl₄induced hepatotoxicity. The antihepatotoxic effect was observed in freshly isolated rat hepatocytes at very low concentrations (80-40 microg/ml). A dose-dependent increase in the percentage viability was observed when CCl4-exposed HepG2 cells were treated with different concentrations of the total alkaloid fraction. Also, the in vivo hepatoprotective effect at 80 mg/kg body weight was comparable with that of the standard Silymarin at 250 mg/kg body weight³². Another study suggested that the hepatoprotective activity of Hygrophila auriculata was due to the presence of phytochemical constitution such as flavonoids and polyphenolic compounds.³³

Nephroprotective activity:

Bibu et al, 2010, studied the therapeutic effect of ethanolic extract of Hygrophila spinosa against gentamycin induced nephrotoxicity in male SD rats. The results revealed that test animals treated with H. spinosa produced significant reduction in lipid peroxide levels through increased free radical scavenging activity when compared with GM treated rats. It also markedly reduced the urea, creatinine levels thereby preventing the primary tubular necrosis³⁴.

Hematopoeitic activity:

Pawar et al, 2006, studied the chloroform extract of the leaves of Asteracantha longifolia at different doses on anaemic albino rats for certain haematological parameters like erythrocyte count, leukocyte count, and haemoglobin count for a period of 7 days against cyclophosphamide. After the treatment, it was found significantly (P <0.05) that erythrocyte and haemoglobin count were improved after continuous cyclophosphamide exposure along with Asteracantha longifolia extract. Also, it was found significant (P <0.001) to increase the bone marrow cellularity and α-esterase positive cells as compared to cyclophosphamide alone treated group. The study proved the ability of A. longifolia as it enhanced the proliferation of stem cells and reversed the effects such as bone marrow suppression and aplastic anemia induced by cyclophosphamide³⁵. Sanju et al, 2015, reported the hematinic effect of Hygrophila spinosa aqeuous extract against the conventional hematinic and combination of both on phenyl-hydrazine induced anemic Wistar rats. The hematological parameters like RBC, hemoglobin, PCV, MCV, MCH, MCHC, serum iron, copper, cobalt, TIBC were analysed and found with increased hemogram profile on treatment with H. spinosa extract in comparison to conventional hematinic³⁶. As iron deficiency anemia is a state of oxidative stress, the antioxidant effect of H. spinosa can overcome the free radical-mediated tissue injury caused by lipid peroxidation. ³⁷

Anti-inflammatory and Analgesic activity:

Al Amin et al, 2012, evaluated the analgesic and anti-inflammatory activities of the ethanol extract of whole plant of Asteracantha longifolia in mice. The analgesic activity determined using hotplate, formalin induced pain and acetic acid-induced writhing test in mice exihibited significant effect on second phase of analgesic response against Tramadol. Anti-inflammatory effect determined by ear swelling induced by croton oil, xylene induced ear oedema, leukocyte migration induced by carrageenan, cotton pellet-induced granuloma formation revealed significant inhibition of swelling against Ibuprofen. Also, the dose-dependent inhibition of abdominal constrictions by the ethanol extract indicated antinociceptive potential of the plant. The extract might have suppressed the synthesis of prostaglandin in the bodies of the animals executing its anti-inflammatory property³⁸.

Antitumor activity:

Sudeshna Saha et al, 2017, described that the crude extract of the plant A. longifolia has shown anti-tumour efficacy in Ehrlich ascites carcinoma and Sarcoma-180, MDA-MB-435S and hepatocarcinogenesis in male Wistar rats. Phytoconstituents Apigenin, Luteol, β- sitosterol and Stigmasterol of H. auriculata had been reported to possess extensive anti-cancer potential and exhibited anti-tumour effects in many different cell lines and in many different types of cancer³⁹.

Effect on Sexual behaviour:

Chauhan et al, 2011, noticed the sexual behaviour of male albino rats administered with ethanolic extracts of A.longifolia. The sexual behaviour assessed by parameters such as mount frequency (MF), intromission latency, mount latency (ML) and post-ejaculatory latency revealed pronounced anabolic effects in treated animals with increased body weight and reproductive organ weights. There was increased spermatogenesis noted with reduction of ML, increase in MF and enhanced attractability towards females. The researchers also observed that there was significant increase in the sperm count as well as fructose levels of seminal vesicles⁴⁰.

3. Parangipattai – Smilax china:

Anti-inflammatory activity:

Cheng Zhong et al, 2017, identified a new triflavanoid, kandelin B-5 from the rhizomes of Smilax china and evaluated the anti-inflammatory activity and noticed that it showed slight IL-1β expression inhibitory activities on Lipopolysaccharides induced THP-1 cells⁴¹.

Antihyperuricemic effect:

Lvyi Chen et al, 2011, explained that ethylacetate fraction of Smilax china exhibited stronger antihyperuricemic activity in hyperuricemic mice. Also, it markedly reversed the serum uric acid level, fractional excretion of urate and blood urea nitrogen to their normal level, and prevented the renal damage against tubulointerstitial pathologies in hyperuricemic rats⁴².

Antiobesity activity:

The anti-obesity activity of Smilax china methanol extract was evaluated using a pancreatic lipase enzyme inhibition assay, and a cell culture model system. The extract effectively inhibited pancreatic lipase enzyme activity in a dose dependent manner and there was significant suppression of insulin, dexamethasone, 3-isobutyl-1-methyl xanthine-induced adipocyte differentiation, lipid accumulation, and triglyceride contents on 3T3-L1 preadipocytes⁴³.

Antidiabetic activity:

Solomon Raju et al, 2012, demonstrated the antidiabetic effect of Smilax china in allaxon induced diabetic rats. The oral administration of root extracts at doses of 200 mg /kg led to a significant blood glucose reduction. The study revealed that the aqueous and alcoholic extracts from Smilax china leaves orally administered for 7 days produced a significant decrease in the blood glucose whereas petroleum extract exhibited very weak anti-diabetic activity⁴⁴.

4. Sarakkondrai – Cassia fistula:

Laxative effect:

Agrawal et al, 2012, observed the laxative effect of dried fruit pulp of Cassia fistula in rats and mice in comparison with castor oil. There was significant increase in intestinal motility. Stimulant laxatives (anthraquinones) were found in fruit pulp of C. fistula which had direct effects on enterocytes, enteric neurons, and GI smooth muscle and stimulated the intestinal motility. The laxative effect of Sun-dried fruit pulp of C. fistula might be due to the presence of anthraquinones with predominant action on intestinal NO formation⁴⁵. A clinical trial was conducted among pediatric population by Mozaffarpur et al, 2012, to study the effect of C.fistula fruit pulp extracts on functional constipation in comparison to a mineral oil. After three weeks of medication, significant improvement was observed in 84% of children treated with C.fistula and 50% in mineral oil group. All measurable criteria improved in both groups. The frequency of defecation seemed better with decreased severity of pain and stool consistency and concluded that treatment with C. fistula extract was most effective than MO in the 3-week treatment of children with functional constipation⁴⁶.

Hypolipidemic activity:

Gupta et al, 2009, found out the effect of ethanolic extract of Cassia fistula legume on serum lipid metabolism in cholesterol fed rats. The animals fed with cholesterol dissolved in coconut oil orally for 90 days were treated with C. fistula legume extract which caused a significant prevention in the elevation of serum total cholesterol, LDL, TGL and phospholipids in a dose dependent manner⁴⁷.

Anti-inflammatory and Antipyretic activity:

Gobianand K et al, 2010, identified the effect of ethanolic extract of C.fistula on rats induced with oedema and pyrexia. The fruit extract significantly inhibited both the carrageenan-induced hind paw oedema and cotton-pellet granuloma in a dose-dependent manner. Also it reduced the vaccine induced elevated body temperature in 30 minutes of drug administration. It was found that C.fistula extract exihibited it to be potentially beneficial in conditions of inflammation and fever⁴⁸.

Antimicrobial activity:

Bhalodia et al, 2012, assessed the hydro-alcohol and chloroform extracts of Cassia fistula fruit pulp for the antimicrobial activity. The antimicrobial activity was determined in both the extracts using agar disc diffusion method. The measurement of growth inhibition zone ranged from 10 mm - 20 mm for all the sensitive bacteria and ranged from 12 mm - 21 mm for fungal strains⁴⁹.

5. Sombu – Foeniculum vulgare:

Antiurolithiatic property:

Poojar et al, 2017, explored the antiurolithiatic property of ethanolic extract of Foeniculum vulgare in male wistar albino rats. The prophylactic model, 100 mg/kg, 200 mg/kg, and 300 mg/kg of Foeniculum extract showed significant reduction in stone formation when compared to untreated control group and the antiurolithiatic effect of F. vulgare was also comparable with standard 750 mg/kg cystone used at dose level of 100 mg/kg and 200 mg/kg. But 300 mg/kg dose showed much therapeutic effect when compared to cystone, justifying its use in the treatment of urolithiasis. The histopathological analysis showed the renal tissues were devoid of leukocyte infiltration along with tubular dilation, swelling and damage⁵⁰. The diuretic effect of F. vulgare lasted for about 24 hours when studied for its diuretic effect and proved it to be a long acting diuretic agent. Also, there observed a non-association with increased urine volume and increased sodium or potassium ion excretion. Thus it possessed a significant diuretic property with its osmotic mechanism.⁵¹

Nephroprotective effect in PCOS:

Sadrefozalayi et al, 2012, studied the renoprotective effect of Foeniculum vulgare in PCOS rats. They observed a positive effect in rats with PCOS treated with aqueous extract of F.vulgare when compared to those treated with estradiolvalerate. After the 4 weeks study, the histopathological and biochemical parameters revealed a significant response at a higher dose level of 150mg/kg of F.vulgare extract. Atrophy of glomerular capillaries with increased Bowman's space and acute tubular necrosis were improved towards the treatment with F.vulgare. There were noticeable healing features in renal tissues and also it decreased the elevated urea and creatinine levels and thus justified F.vulgare as renoprotective phytoestrogen in the treatment of PCOS when compared to estradiol which lead to renal toxicity⁵².

Analgesic and anti-inflammatory activity:

Elizabeth et al, 2014, validated the analgesic and anti-inflammatory property of F.vulgare on wistar rats and swiss albino mice. The ethanolic extract of F.vulgare produced significant (p<0.001) dose-dependent inhibition of pain response at 50,100 and 200 mg/kg. Also, it elucidated significant (P< 0.001) dose dependent inhibition of oedema development in the carrageenan induced inflammation. Thus the anti-inflammatory and analgesic effects of F.vulgare were validated⁵³.

Oculohypotensive effect:

Agarwal et al, 2008, evaluated the aqueous seed extract of Foeniculum vulgare in rabbits with normal intraocular pressure and with experimentally elevated IOP (Glaucoma). A maximum mean (31.29%) lowering of intraocular pressure was observed in steroid induced model of glaucoma. Hence, the aqueous extract of F. vulgare possessed significant oculohypotensive activity, which was found appreciable to that of thimolol⁵⁴.

Antimicrobial activity:

Dolly Agarwal et al, 2017, investigated the antimicrobial potency of F. vulgare against gram positive and gram negative bacteria. The aqueous seed extract of F. vulgare showed strongest antifungal activity as compared to griseofulvin, a reference fungicidal agent. Dillapional, a phenylpropanoid derivative from F. vulgare stem and scopoletin, a coumarin derivative was found to be marginally antimicrobial agents, identified in the study⁵⁵.

6. Manathakkali – Solanum nigrum:

Antimicrobial activity:

Pankaj kumar et al, 2016, evaluated the antimicrobial activities of S. nigrum leaves, fruits and stems extract against various pathogenic bacteria. Among different extracts, S. nigrum leaves water extract showed significant inhibition zone (21.30 ± 1.50mm) at 50 mg/ml against P.aeruginosa. While ethanolic extract of leaves showed effective zone of inhibition (18.30± 0.58mm) at 50 mg/ml against E. coli. The researchers identified it to be a broad spectrum antimicrobial agent against various pathogens⁵⁶.

Nephroprotective and Antiurolithiatic activity:

Yesu babu et al, 2013, evaluated the nephroprotective activity of Solanum nigrum leaves in gentamycin induced nephrotoxic rats along with the antiurolithiatic activity in the same rats fed with calculi inducing diet. Groups treated with S.nigrum extract showed a significant increase in the levels of antioxidant enzymes such as SOD and Catalase when compared to negative control group and decrease in lipid peroxidation. The plant extract at doses of 200mg/kg and 400mg/kg showed significant decrease in total protein, urea, creatinine and significant increase in a dose dependent manner at p<0.05. The antiurolithiatic activity of Solanum nigrum might be due to its diuretic activity which was attributed to the presence of glycoprotein’s and flavanoids. The study revealed that S.nigrum significantly reversed the tubular necrosis and renal damage induced by Gentamycin and also it caused a significant reduction in urinary excretion of calcium and oxalate and thus reduced the supersaturation of urine⁵⁷.

Anti-inflammatory activity:

Aryaa and Viswanathswamy (2017), validated the anti-inflammatory activity of S.nigrum in carrageenan and cotton pellet induced oedema. The hydroalcoholic extract of whole Solanum nigrum plant showed a promising anti-inflammatory activity in both acute and sub-acute stages of inflammation by decreasing the paw volume and controlling the secretion of pro-inflammatory mediators⁵⁸.

Effect in Diabetic Nephropathy:

Azarkish et al, 2017, experimentally found that the extract of S.nigrum was effective in the treatment of Diabetic nephropathy in Streptozotocin induced diabetic rats against standard insulin treatment. They reported that there was a significant decrease in weight of enlarged kidneys throughout the period of study, but the plant extract elucidated more successful in 8 weeks than insulin. Kidney tissue damage score was decreased by the extract along with the reduction in creatinine, BUN and urea level, whereas insulin did not change it. The extract decreased the urine protein level but insulin treatment increased it significantly. Also, they have validated that it could significantly decrease the alteration in vascular reactivity and vessel atherosclerosis as cardiovascular complications of diabetes⁵⁹.

7. Surai – Lagenaria siceraria:

Antiurolithiatic activity:

Takawale et al, 2012, evaluated the effect of Lagenaria siceraria fruit extract on sodium oxalate induced urolithiatic rats against the standard drug cystone. The results revealed the remarkable changes in urinary output, renal parameters and crystal deposition. The urinary output was 22.5 ± 4.209 mL/day/rat treated with L.siceraria and 17 ± 3.296 mL/day/rat treated with cystone. Also, it reversed the elevated renal parameters caused by sodium oxalate and there was medium deposition of crystals in the renal interstitium. The presence of terpenoids and flavonoids might be playing an effective role in preventing the aggregation of crystals⁶⁰.

Diuretic activity:

Jayasree et al, 2014, studied the diuretic and natriuretic potential of L.siceraria seed extracts in albino rats. They found that the seed extract of Lagenaria siceraria at 100mg/kg and 200mg/kg produced significant (P <0.05) natriuretic and saluretic activity with increased potassium elimination and decreased urinary output against the standard drug hydrochlorothiazide. The researchers concluded that all other parts of the plant were reported to have diuretic property except the seeds which were found to possess antiduretic property⁶¹.

Cardioprotective activity:

Manglesh kumar Singh et al, 2012, demonstrated the effect of Lagenaria siceraria seed extract on doxorubicin induced cardio toxicity in wistar rats in comparison with simvastatin as a standard drug. At a dose level of 400mg/kg, the plant extract significantly produced positive changes in the elevated cardio biomarker enzymes LDH, CK, CK-MB and total protein and antioxidants superoxide dismutase, catalase, glutathione and lipid peroxidation. Also the histopathological studies in animals treated with L.siceraria extract revealed nearly normal appearance of myocardium with very mild inflammatory cell infiltrate and there was absence of necrosis nioticed in the myocardium compared to those treated with simvastatin. Thus it significantly ameliorated DOX induced cardio toxicity in rats in a dose dependant manner⁶².

Anti-inflammatory activity:

Saha et al, 2015, evaluated the methanolic extract of aerial parts of Lagenaria siceraria for the anti-inflammatory and antinocioceptive activities in rat model. The results revealed it so positive for its antinociceptive activity at a dose level of 400mg/kg in comparison with the standard drug indomethacin. It also inhibited rat paw ooedema in acute inflammatory model with a significant suppression in granuloma formation⁶³.

8. Vellari – Cucumis sativus:

Antiurolithiatic activity:

Pethakar et al, 2017, evaluated the lithotriptic effect of hydroalcoholic extract of Cucumis sativus on ethylene glycol induced urolithiatic rats against the standard drug cystone. The animal groups treated with the extract showed significant dose dependent activity, although finer fragments of renal stones were noticed in lower and medium dose regimen. Serum creatinine, uric acid and BUN were decreased in the treated group with C.sativus extract as that of cystone. The rate of glomerular filtration was increased thereby enhancing the effective diuresis in the C.sativus treated group. Also, it decreased the nephritic damage and minimized the concentrations of stone forming elements in a dose dependant manner⁶⁴.

Effect on Heat stress:

Subasini et al, 2013, investigated the effect of Cucumis sativus extract on stress induced by heat by estimating various biochemical parameters like lipid profile, oxidative enzyme, glucose and protein in the wistar rats exposed to a temperature of 40°C (for an hour) which were pretreated with Cucumis sativus extract at the dose of 250 and 500mg/kg body weight for 2 days. The C.sativus seed extract at the dose of 500mg/kg, body weight exihibited significant anti heat stress activity. There was a marked decrease in serum glucose concentration (P<0.01) and a significant increase in serum protein concentration (P<0.01). The increased malondialdehyde and other unsaturated aldehydes generated by heat was found to be decreased significantly (P<0.01). Also, it prevented the lipid peroxidation and thereby limited the release of free radicals and prevented the oxidative stress⁶⁵.

Nephroprotective activity:

Prasanthi et al, 2016, evaluated the protective effect of hydroalcoholic extract of seeds of Cucumis sativus against cisplatin and gentamycin-induced nephrotoxicity in male Albino wistar rats. There was a significant reduction in the levels of serum creatinine, total protein, BUN and increased creatinine clearance. Treatment with C.sativus had decreased the lipid peroxidation and increased the antioxidants superoxide dismutase, catalase and Glutathione reduced in a dose dependent criteria. Thus, it revealed both curative and prophylactic regimens by producing regenerative changes in the renal tissues⁶⁶.

9. Kadukkai – Terminalia chebula:

Anti-inflammatory and Antioxidant activity:

Bag et al, 2013, evaluated the anti-inflammatory effect of Terminalia chebula in both in vitro and in vivo models. The standardized extract at 250 mg/kg, produced 69.96% reduction in Carrageenan induced rat paw oedema and a significant protective effect of 96.72% on human RBC membrane stability. T. chebula fruit extract significantly reduced the in vivo formation of TBARS in carrageenan-induced rat liver with IC₅₀ 94.96 mg/kg and also in vitro radical scavenging activities in DPPH assay method with IC₅₀ 42.14 µg/ml. When the human red blood cells were subjected to hypotonic stress, the release of hemoglobin from RBC was prevented and there exihibited a membrane stabilization. The fruit extract also strongly inhibited in vivo lipid peroxidation in rat liver in the study⁶⁷. Due to the antioxidant property, Terminalia chebula had been studied for the potent cholesterol lowering activity as it was used beneficially in reducing the excess fat deposition⁶⁸.

Antimicrobial activity:

Giri et al, 2013, identified the antimicrobial activity of aqueous extract of T.chebula by agar well diffusion method against both gram positive and negative and fungal strains. Based on the zone of inhibition they demonstrated that it exihibited a highest zone of inhibition (26.56±0.28mm) against Proteus mirabilis. Also, it produced effective inhibition against potent microbes like Klebsiella pneumoniae (23.6±0.36mm) and Salmonella typhimurium (22.66±0.15mm). The T.chebula extract produced good antimicrobial activity against oral bacterial strains predominantly thus substantiating it as an effective broad spectrum antimicrobial agent⁶⁹.

Antiurolithiatic activity:

Pawar et al, 2012, investigated the antiurolithiatic potential of aqueous extract of fruit of Terminalia chebula in Wistar albino rats. At the dose levels of 100mg/kg and 200mg/kg against ethylene glycol induced calcium oxalate urolithiasis in rats, it produced an effective decline in the elevated levels of oxalate and phosphate in urine as well as kidney tissue homogenate. The extract supplementation also prevented the elevation of serum creatinine, uric acid and blood urea nitrogen. Histopathological study revealed that extract reduced histological changes and retained the normal architecture of kidney tissue⁷⁰. Karunasree Varicola et al, 2017, investigated the different extracts of T.chebula for its antiurolithiatic activity and found that chloroform extract possessed a highly positive effect when compared with standard drug and concluded that it might be because of the non-polar active principles contained in the extract⁷¹.

Cytoprotective activity:

Tayal et al, 2012, carried out the antilithiatic activity of Terminalia chebula along with the renal epithelial cells protectivity in cell line studies. There was 95.84% inhibition of Calcium oxalate nucleation with the increasing concentration of the plant extract. The aqueous extract prevented the injury in MDCK and NRK-52E cells caused by oxalate exposure for a period of 48 hours, in a dose-dependent manner. The LDH release was significantly decreased to the level of 28.2% in the treatment with 80μg/mL of extract in NRK-52E cells. MDCK cells also showed the same pattern with 78.6% LDH release in oxalate injured cells which got decreased significantly to 26.7% with the highest concentration of the plant sample. The viability of cells increased from 41.3% to 60.4% when tested with NRK-52E cells and to 71.3% when tested with MDCK cells as compared to 52.9% viability in oxalate injured cells⁷².

10. Nellivattral - Phyllanthus emblica:

Antigout activity:

The extracts of Phyllanthus emblica fruits were subjected for the evaluation of antigout activity by Sarvaiya et al (2015) with repeated administration of potassium oxonate in rat model for a period of 28 days. Animals groups which were given aqueous and alcoholic extracts of P. emblica revealed significant (p<0.05) reduction in level of serum creatinine, uric acid, BUN, and Xanthine oxidase enzyme level in dose-dependent manner as compared to gout control group. Gouty rats treated with aqueous and alcoholic extracts of P. emblica fruits at 200 and 400 mg/kg body weight showed significant increase in mean platelets counts as compared to control group and the histopathological study also revealed the reversal in necrotic and congested renal epithelium⁷³.

Nephroprotective activity:

Tasanarong et al, 2014, identified the protective effect of Phyllanthus emblica in contrast-induced acute kidney injury (CI-AKI) with respect to the antioxidant property in rat models. When the animals were pre-treated with the fruit extract for five days at a dose level of 250 and 500 mg/kg/day, it exerted significant renoprotective effects in rats with CI-AKI. P. emblica extract significantly (P < 0.05) preserved plasma total antioxidant capacity, renal superoxide dismutase and catalase activities, thereby ameliorated the renal function and attenuated the severity of pathological damage with a significant decrease in malondialdehyde (MDA). Thus, it possessed a significant antioxidant property in protecting the renal tissues⁷⁴.

Effect on Struvite stones:

Bindhu et al, 2015, studied the effect of Phyllanthus emblica extract on the growth of struvite stones in in vitro model. They found that the average numbers of crystals grown per vessel in the P.emblica extract added vessel were found to be 11 ± 2.3 when compared to the control group which showed 28 ± 3.9. It was observed that nucleation of struvite crystals was controlled and only a few numbers of crystals were obtained in the Phyllanthus emblica extract added system. Also, the total weight was estimated to be 1.6 ± 0.3 g in the control group whereas the average number of crystals grown in the extract added group was estimated to be 1.4 ± 0.2 g. Thus, it revealed a significant difference between control and extract (p < 0.05). It clearly indicated that P.emblica reduced the nucleation of struvite crystals and hence had an inhibiting effect on struvite crystal formation. About 60% reductions in the total number of crystals were noted⁷⁵.

Immunomodulatory effect:

Liu et al, 2012, evaluated the immunomodulatory properties and anticancer potential of phenolic compounds from P.emblica fruit by in vitro proliferation assay. The effect on splenocyte proliferation and the cytotoxicity to both human breast cancer cell (MCF-7) and human embryonic lung fibroblast cell (HELF) were determined by the MTT method. Significant stimulatory effects (P < 0.05) were found for the phenolic compounds, geraniin and isocorilagin. The researchers reported that the assay of anticancer activities suggested that geraniin and isocorilagin exhibited higher cytotoxicities than other compounds against MCF-7 with IC₅₀ of 13.2 and 80.9 µg/ml, respectively. Isocorilagin exhibited a strong cytotoxicity to HELF cell with IC₅₀ of 51.4 µg/ml. Geraniin, quercetin, kaempferol and their glycosides had weak cytotoxicity against HELF cells. Paclitaxel showed a strong cytotoxicity to MCF-7 and HELF with IC50 of 6.8 and 14.5 µg/ml, respectively. It was reported that the antitumour activity of these compounds might be achieved by immunomodulatory properties of P.emblica⁷⁶. As this fruit is rich in Vitamin-C, it plays an important role as antioxidant and hence it is used in the management of urinary tract infections and other inflammatory conditions⁷⁷.

11. Thandrikkai - Terminalia bellerica:

Nephroprotective activity:

Fatima et al, 2016, evaluated the protective effect of Terminalia bellerica on Gentamycin induced nephrotoxicity in albino rats. The ethanolic and aqueous extracts of dried stem of T.bellerica were injected in nephrotoxic rats and after 15 days of study, results were analysed for the renal parameters and the antioxidant enzyme levels. Treatment with standard, ethanolic and aqueous extract of T. bellerica showed significant antioxidant effect, by producing increase in catalase levels compared to control. The elevated renal parameters serum urea, creatinine and uric acid were significantly decreased in the treated group and the elevated oxidative stress markers were also decreased. Glomerular congestion, disruption of glomerular capillaries, vacuolar degeneration of tubular epithelial cells caused by gentamycin toxicity was reversed with ethanolic extract of T. bellerica. Treatment with aqueous extract of T. bellerica also reversed the apoptosis like alterations in the histopathological studies. Thus the stem extract of T.bellerica exihibited a remarkable alterations in the gentamycin induced nephrotoxicity and proven it to be potent nephroprotective agent⁷⁸.

Antiurolithiatic activity:

Santosh kumar Maurya et al, 2015, investigated the antiurolithiatic potential of T.bellerica fruits on ethylene glycol induced urolithiasis in rat models. When the animals were subjected for acute oral toxicity with a maximum dose of 4000mg/kg body weight, they observed that there was no abnormal behavioural pattern throughout the study period. The treatment with methanolic extract of T.bellerica fruits significantly (p < 0.05) decreased the pH of urine near to neutral in calculi induced animals. At the dose levels of 100 and 200mg/kg, the extract did not produce any significant changes in the reduction of calculi and renal parameters. The fruit extract at 400 mg/kg showed significant (p < 0.05) reduction in the urinary excretion of calcium, phosphate and oxalate. Also it remarkably reduced the serum uric acid and urea levels comparable with cystone and also the size of the oxalate crystals were also decreased. The researchers concluded that the antiurolithiatic effect of T.bellerica might be due to the presence of flavonoids and saponins⁷⁹.

Antiangiogenic activity:

Shivakumar et al, 2010, investigated the antiangiogenic activity of fruit pericarp extract of T.bellerica using Ehrlich ascites tumor (EAT) model in mice using CAM (Chorioallantoic membrane assay) and ELISA. After 12 days of treatment, the researchers sacrificed the animals and observed for peritoneal angiogenesis, secretion of ascites, cell number, microvessel density and secretion of VEGF (Vascular Endothelial Growth Factor). They observed that the animals which received aqueous extract of T.bellerica showed 2.8 folds reduction in the EAT cell number (0.65 x 108 cells/ mouse) compared with that of untreated animals. Also, there was 80.78% reduction in body weight of the animals. The volume of ascitic fluid was decreased to an extent of 75.43% (2.0±0.10ml) when compared to that of untreated EAT bearing animals (8.5±0.15ml). The neovascularization in the peritoneum of T.bellerica extract treated mice was extensively inhibited. The microvessel density counted in the peritoneum of treated group revealed a significant reduction of 82.2% (3.21±0.13) when compared with the untreated group which was 18.09±0.02 cells/ HPF. There was also VEGF reduction in the mice treated with T.bellerica extract⁸⁰.

The phyto-constituents of the individual drugs in Neermulli Kudineer formulation are listed in Table:2

CONCLUSION:

From the scientific literatures, it is understood that the ingredients of polyherbal formulation Neermulli Kudineer possessed predominantly diuretic, antiurolithiatic, antimicrobial, anti-inflammatory and antioxidant activities, moderately immunomodulatory, hepato and nephroprotective and antiobesity activities and minimally antidiabetic, antihypertensive, hematinic and spermatogenic activities. This substantiated the traditional therapeutic uses and applications mentioned in the classical Siddha literatures as given in Table 1. The drugs in the NMK formulation are of chiefly sweet (Inippu) in taste followed by astringent (Thuvarppu) and bitter (Kaippu) taste. Thus, it mitigates the vitiated vatham and kabam humor responsible for the clinical manifestations such as suppression of bowel movements, urinary retention, oedematous swelling, ascites and painful inflammatory conditions through effective diuresis and laxation. Also, it pacifies the deranged Pitham humor responsible for the clinical manifestations such as anorexia, anaemia, abdominal flatulence, indigestion, oliguria, dysuria, leucorrhoea, diabetes and impotency ^{2, 9}. In Siddha system of medicine, it is mentioned that every single herb possesses specific medicinal properties and therapeutic values and this may vary when given in a combined form or as a formulation. From the literatures reviewed, the therapeutic indications mentioned for Neermulli Kudineer as a formulation are virtually same as that of its individual herbs which may be due to its synergetic effect. Thus, the traditional and scientific literature evidences in this review, enlightened the diuretic and antiurolithiatic significance of Neermulli Kudineer and proved it to be a classical Siddha formulation in the management of ascites, oedema, swelling and absolute suppression of urine. As phytotherapies, phytomedicine and new chemical entities discovery are growing rapidly in recent days⁸¹, this review may pave a platform for conducting various preclinical and clinical studies in NMK formulation as a whole to substantiate its clinical efficacy.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 23.08.2018 Modified on 19.10.2018

Research J. Pharm. and Tech 2019; 12(1): 445-460.

DOI: 10.5958/0974-360X.2019.00081.7

S. No.	Tamil Name and Common Name	Botanical Name	Parts Used	Therapeutic Actions in Siddha	Therapeutic Uses in Siddha
1.	Nerunjil (Small Caltrops)	Tribulus terrestris L.	Whole plant	Coolant, Diuretic, Demulcent, Tonic, Virility enhancer, Astringent, Diuretic.	Neerkattu, Sottuneer, Kalladaippu, Vellai, Siruneererichal, Sadhaiyadaippu, Neervetkai, Kiricharam, Mukkuttram.
2.	Nellikai (Emblica myrobalan)	Phyllanthus emblica L.	Dried fruit	Laxative, Coolant, Diuretic, Rejuvenator.	Vaandhi, Verinoi, Pramegam, Aankuripun, Neerchurukku, Kaamalai, Peruvayiru, Soolai.
3.	Neermulli (Long leaved barleria)	Asteracantha longifolia L. (Nees)	Whole plant	Demulcent, Diuretic,Tonic, Coolant, Aphrodisiac.	Sobai, Peruvayiru, Oothal, Neerkattu.
4.	Parankisakkai (China root)	Smilax china L.	Root tuber	Aphrodisiac, Anti-syphilitic, Purifier, Restorative.	Soolai, Neerizhivu, Neervetkai, Vettai, Uppisam, Karappan, vadhanoi, Pun, Pilavai.
5.	Manathakkali (Black Night shade)	Solanum nigrum L.	Dried fruit	Diuretic, Diaphoretic, Expectorant, Tonic	Neerchurukku, Neerkovai, Peruvayiru, Suvayinmai, Vaandhi, Kozhai.
6.	Sarakkondrai (Indian Laburnum, Purging Cassia)	Cassia fistula L.	Fruit pulp	Purgative, Vermifuge.	Vellai, Malakattu, Kudalvali, external application for Neerkattu
7.	Sombu (Fennel)	Foeniculum vulgare Mill.	Dried fruit	Carminative, Appetiser	Seriyamai, Eeral noi, Eraippu, Erumal, Soothagavaayu, vayitruvali, uppisam.
8.	Vellari (Cucumber)	Cucumis sativus L.	Seeds	Diuretic, Demulcent, Coolant	Kalladaippu, Sadhaiyadaippu, Kiricharam, Mega noi, Neerkattu, Neerpuzhai vedippu
9.	Surai (Bottle gourd)	Lagenaria siceraria (Mol) Standl	Stem climber	Diuretic, Coolant.	Veekkam, Peruvayiru, Neerkattu, Verinoigal.
10.	Kadukkai (Myrobalan)	Terminalia chebula Retz.	Dried fruit (Pericarp)	Digestive, Expectorant, Laxative, Appetiser, Nutrient, Rejuvenator	Kamalai, Kannoigal, kuruthiazhal, Peruvayiru, Kalladaippu, Moothirakiricharam, Sobai, Paandu, Moolam, Vellai, Megam, Veekkam, Malakkattu.
11.	Thandrikai(Beleric Myrobalan)	Terminalia bellerica (Gaertn.) Roxb.	Dried fruit (Pericarp)	Expectorant, Laxative, Astringent, Tonic.	Aan kuripun, Kurudhiazhalnoi, Vellai, Thondaikammal, Mukkuttram thannilai.

S.No	Botanical Name	Phyto-constituents
1.	Tribulus terrestris L.	Terrestriamide,Tribulusamide A,B; Tribulosin, Protodioscin saponin C, Terrestroside F; Quercetin-3-gentiobioside-7 glucoside; moupinamide, tribulosaponin
2.	Phyllanthus emblica L.	Ascorbic acid, gallic acid, ellagic acid, L-mallic acid-2-O-gallate, mucic acid-2-O-gallate, tannins.
3.	Asteracantha longifolia L. (Nees)	Lupeol, stigmasterol, isoflavone glycoside,apigenin 7-O-glucuronide, Linoleic acid, Mn, Mg, Zn, Ca, Fe, Ni, Cr, Na,K, Al, Cu.
4.	Smilax china L.	Sarsaponin, parallin, β-sitosterol, daucosterol, stigmasterol, isoseryl-S-methyl-cysteamine sulphoxide.
5.	Solanum nigrum L.	Gallic acid, proto-catechuic acid, caffeicacid, epicatechin, rutin, naringenin, solamargine, solasonine and solanine
6.	Cassia fistula L.	Fistulic acid, epicatechin, aspartic acid, glutamic acid, procyanidin-B-2, leucine, methionine, tryptophan, sucrose, galactoserhein.
7.	Foeniculum vulgare Mill.	E-anethole, fenchone, syringin, bergapten, methyl chavicol, cis-myabenol and its glycosides, icaviside A, adenosine.
8.	Cucumis sativus L.	Fixed oil, Sterols, clerosterol, avenasterol, stigmasterol, campesterol, 25(27)-dehydroporiferasterol, and isofucosterol.
9.	Lagenaria siceraria (Mol) Standl	Cucurbitacin B, Saponins, Flavanoides, Tannins, Triterpenoids, isovitexin, isoorientin, saponarin.
10.	Terminalia chebula Retz.	Gallic acid, chebupentol, arjunolic acid, arjungenin, terminoic acid, p-coumaric acid, ferulic acid, tannins, chebulic acid, ellagitannin terchebulin.
11.	Terminalia bellerica (Gaertn.) Roxb.	Gallic acid, chebullagic acid, belleric acid, bellericanin, phyllembin, termilignan, thaninilignan ,belericoside, ellagic acid, β-sitosterol.